國家衛生研究院 NHRI:Item 3990099045/4778
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4778


    Title: Deficiency of glycine N-methyltransferase results in deterioration of cellular defense to stress in mouse liver
    Authors: Liao, YJ;Chen, KH;Huang, SF;Chen, TL;Wang, CK;Chien, CH;Tsai, TF;Liu, SP;Chen, YMA
    Contributors: Division of Molecular and Genomic Medicine
    Abstract: Purpose: Previously, we reported that glycine N-methyltransferase (GNMT) interacts with benzo[a]pyrene (BaP) and inhibits BaP-DNA adducts formation. In addition, Gnmt knockout (Gnmt(-/-)) mice developed chronic hepatitis and hepatocellular carcinoma (HCC). The aims of this study were to understand the gene expression profile of Gnmt(-/-) mice and to study the interaction between BaP and GNMT deficiency in vivo. Experimental design: Gene expression profiles of Gnmt(-/-) mice were analyzed by 2-D PAGE and real-time PCR. Both wild-type and Gnmt(-/-) mice were challenged with BaP and sacrificed at the age of 13 months. Results: Compared with the wild-type mice, proteins involved in the anti-oxidation/detoxification response, glycolytic energy metabolism and one-carbon metabolism pathways were down-regulated significantly in Gnmt(-/-) mice. Malondialdehyde assay showed that lipid peroxidation was significantly increased in the Gnmt(-/-) mice liver. H2O2 treatment demonstrated that the survival rate of HuH-7 cells overexpressing GNMT was significantly higher than the controls. BaP challenge experiments showed that 71.4% (5/7) of male and all (7/7) female Gnmt mice developed HCC, while only 16.7% (1/6) of male and 20% (1/5) of female wild-type mice had HCC. Conclusion and clinical relevance: GNMT regulates genes related to detoxification and anti-oxidation pathways. BaP is a liver cancer carcinogen especially during GNMT deficiency.
    Date: 2010-04
    Relation: Proteomics Clinical Applications. 2010 Apr;4(4):394-406.
    Link to: http://dx.doi.org/10.1002/prca.200900074
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1862-8346&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000277221700005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77953718800
    Appears in Collections:[Shiu-Feng Kathy Huang] Periodical Articles

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